Reparameterization of All-Atom Dipalmitoylphosphatidylcholine Lipid Parameters Enables Simulation of Fluid Bilayers at Zero Tension

Molecular dynamics (MD) simulations of dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using the CHARMM27 force field in the tensionless isothermal-isobaric (N PT) ensemble give highly ordered, gel-like bilayers (20) with an area per lipid of ~48 Ų (31). To obtain fluid (L) phase properties of DPPC bilayers represented by the CHARMM energy function in this ensemble, we reparameterized the atomic partial charges in the lipid head group and upper parts of the acyl chains. The new charges were determined from the electron structure using both the Mulliken method and the restricted electrostatic potential (RESP) fitting method (5). We tested the derived charges in MD simulations of a fully hydrated DPPC bilayer. Only the simulation with the new RESP charges shows significant improvements compared with simulations using the original CHARMM27 force field resulting in an area per lipid of 60.4 ± 0.1 Ų. Compared to the 48 Ų, the new value of 60.4 Ų is in fair agreement with the experimental value of 64 Ų (43). Also the simulated order parameter profile and electron density profile are in satisfactory agreement with experimental data. Thus, the biologically more interesting fluid phase of DPPC bilayers can now be simulated in all-atom simulations in the N PT ensemble by employing our modified CHARMM27 force field. Copyright © 2007 by the Biophysical Society.